B regulatory cells in cancer

Balkwill, Frances R.; Montfort, Anne; Capasso, Melania

doi:10.1016/j.it.2012.10.007

Cited by 115 publications

(92 citation statements)

References 38 publications

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“…Finally, our finding that cases exhibited a significantly elevated frequency of Bregs, which can inhibit anti-tumor immunity, corroborates reports in other malignancies [33]. Although we did not find an elevated Tregs frequency, it is feasible that Bregs driven Treg differentiation can profoundly compound the anti-tumor immunity inhibitory milieu.…”

Section: Discussionsupporting

confidence: 90%

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Siewe

Pham

Cohen

et al. 2015

AIDS

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Objectives-In Antiretroviral therapy (ART)-treated subjects, to determine if AIDS-related NonHodgkin Lymphoma (AIDS-NHL) is preceded by: i) elevated frequency of potentially malignant abnormal activated/ Germinal center (GC)-like B cells, ii) elevated serum prevalence of B-cell stimulatory TLR-ligands resulting from HIV-infection associated microbial translocation, iii) dysregulated B-cell TLR expression/signaling and iv) perturbations in the frequency of immunoregulatory cells.Design-A case-control study nested with a cohort study of HIV-infected women.Methods-Pre-diagnostic AIDS-NHL cases (n=14, collected 1-12 months pre diagnosis) and controls (n=42) from the Women's Interagency HIV Study (WIHS) cohort, were matched for HIV and ART status, age, race, and CD4 lymphocyte count. Serum levels of TLR ligands, the prevalence of malignancy-associated abnormal activated/GC-like (CD19 + CD10 + CD71 + CD86 + AID + ) B cells, TLR2 expression on B cells, expression of TLR2-modulating micro-RNA, and the frequency of regulatory T and B cells were assessed. Conclusions-Our findings suggest that increased microbial translocation and dysregulated TLR expression/signaling, coupled with an elevated frequency of Bregs precede the diagnosis of AIDS-NHL in HIV-infected ART-treated subjects. Results-Diagnosis HHS Public Access

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Section: Discussionsupporting

confidence: 90%

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Siewe

Pham

Cohen

et al. 2015

AIDS

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“…In light of the ongoing phase Ib/II clinical trial (NCT02403271) using combination PD-L1 inhibitor (durvalumab) and BTK inhibitor (ibrutinib) for treatment of NSCLC, and the ambiguity as to the role of B cells in NSCLC, we thought a deeper analysis of tumor-associated B cells was warranted. B cells as components of TLSs are good prognostic factors in cancer (27), whereas IL-10-producing Bregs are regarded as negative (28). We found TLSs in 20 of 22 NSCLCs assayed, but there was no association between "hot" or "cold clusters (Supplemental Figure 7E).…”

Section: Discussionmentioning

confidence: 78%

“…This exploratory data set provides a proof of principle for the single-cell expression profiling of tumor-infiltrating B cells and a glimpse at their transcriptional profile. Unlike FOXP3 + Tregs, it has been reported that Bregs do not irreversibly lineage commit at an early developmental point but can adopt a regulatory phenotype at various stages along the B cell developmental continuum (28). The IL-10-producing B cells we analyzed by single-cell RNAseq resemble a plasma cell phenotype, with hallmarks of MYC activation and oxidative metabolism ( Figure 8, B and C).…”

Section: Cd38mentioning

confidence: 91%

Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

Lizotte¹,

Ivanova²,

et al. 2016

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BACKGROUND.Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS.We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS.Cytometric profiling identified an immunologically "hot" cluster with abundant CD8 + T cells expressing high levels of PD-1 and TIM-3 and an immunologically "cold" cluster with lower relative abundance of CD8 + T cells and expression of inhibitory markers. The "hot" cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the "hot" cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS.Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.

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“…17,18 More recently, populations of regulatory B cells (Bregs) able to dampen the immune response have been highlighted as a "driving force" in autoimmune diseases, cancers, and transplantation. [19][20][21][22][23] However, their nature, origin, phenotype, and mode of action in humans remain little known.…”

mentioning

confidence: 99%

Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties

Chesneau¹,

Michel²,

Dugast³

et al. 2015

Journal of the American Society of Nephrology

137

125

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Whereas a B cell-transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells have in this tolerance has not been reported. In this study, we analyzed the role of B cells from operationally tolerant patients, healthy volunteers, and kidney transplant recipients with stable graft function on T cell suppression. Proliferation, apoptosis, and type I proinflammatory cytokine production by effector CD4 + CD25 2 T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells inhibit CD4 + CD25 2 effector T cell response in a dosedependent manner. This effect required B cells to interact with T-cell targets and was achieved through a granzyme B (GzmB)-dependent pathway. Tolerant recipients harbored a higher number of B cells expressing GzmB and displaying a plasma cell phenotype. Finally, GzmB + B-cell number was dependent on IL-21 production, and B cells from tolerant recipients but not from other patients positively regulated both the number of IL-21 + T cells and IL-21 production, suggesting a feedback loop in tolerant recipients that increases excessive B cell activation and allows regulation to take place. These data provide insights into the characterization of B cell-mediated immunoregulation in clinical tolerance and show a potential regulatory effect of B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.

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B regulatory cells in cancer

Cited by 115 publications

References 38 publications

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties

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